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Biomedical subjects

L Laroche

Publications and source records attributed to L Laroche.

At least 19 recordsLinked to original sources
PubMed1992

Interleukin-7 is a growth factor for Sézary lymphoma cells.

Sézary syndrome is a cutaneous T cell lymphoma characterized by infiltration of the skin by CD4+ cells. These cells generally respond poorly to mitogens and T cell activators. We have studied the action of IL1 to IL4, IL6, and IL7 on the proliferation of Sézary cells from 12 patients. With the exception of IL2 and IL7, the cytokines studied had no proliferative effect on these cells. Whereas IL2 had only a low proliferative capacity (two- to threefold increase) on peripheral blood mononuclear cells, recombinant IL7 constantly induced a very significant (3-40-fold increase) proliferative response, and was used successfully to generate cell lines in three out of eight cases. Growth of Sézary cell lines was shown to be strictly dependent on IL7, and after 2-5 wk of culture presented a switch to a homogeneous phenotype CD3+4+8-7- (except for one line that remained CD7+), with a typical morphology of Sézary cells. Their tumoral origin was demonstrated by the expression of the same T cell receptor-beta gene rearrangement as the patients' T cells. Importantly, cultured normal epidermal keratinocyte supernatants could support the growth of our Sézary lines. Furthermore, the proliferative activity contained in these supernatants was completely blocked by a monoclonal anti-IL7 antibody. These results suggest that IL7 may, therefore, represent an important cytokine in the physiopathology of cutaneous T cell lymphoma.

Adult↗
PubMed1992

In vitro kinetics of 8-methoxypsoralen penetration into human lymphoid cells.

Extracorporeal photochemotherapy (ECPC) requires ex vivo UVA irradiation of blood lymphocytes during the time of the theoretical peak 8-methoxsalen (8-MOP) concentration. The aims of this study were to determine the mechanism of cellular uptake of 8-MOP, its possible saturation and the time needed to reach maximal concentration (Tmax) in lymphoid cells. 8-MOP was measured by liquid chromatography in the supernatant of lymphoid cell suspensions incubated with a known amount of 8-MOP. The kinetics of cellular uptake were determined and showed that equilibrium had already been reached after 2 min and remained constant for at least 60 min. The uptake was independent of temperature (4, 25 and 37 degrees C) and was proportional to the 8-MOP concentration in the supernatant. This indicated that 8-MOP penetrated into lymphoid cells by passive diffusion, rather than by active transport or facilitated diffusion, and was thus a non-saturable process. In addition, intracellular metabolism was negligible. These findings demonstrated that the plasma and lymphocytic Tmax were reached simultaneously and statistical analysis showed them to be significantly correlated, thereby validating the standard ECPC protocol for drug ingestion and lymphocyte irradiation.

Humans↗
PubMed1992

[Behavioral asymmetry in BALB/cCF mice with corpus callosum abnormalities].

The possible homology between anomalies of the corpus callosum in mice and in humans remains questionable. The small number of existing behavioural studies in mice have not shown effects, at the behavioural level, of the absence or reduction in size of the corpus callosum. We therefore examined the development, during the first 3 weeks of postnatal life, of a number of simple reflex and integrative responses in the members of a sample of 101 BALB/cCF mice; at autopsy carried out at 50 days of age, 29 mice showed anomalies of the corpus callosum (total absence or an area less than 0.75 mm2). Asymmetry of the development of these responses was measured either as the proportion of animals showing asymmetrical appearance of responses on the left and right sides, and as the delay between appearances on the left and right sides in "asymmetrical" mice. Both measures decreased over the first 15 postnatal days, at the same rate in normal and abnormal mice; in each case the decrease is better described by a second-order, quadratic, function than by a simple linear function. We therefore conclude that the integrity of the corpus callosum is not necessary for the normal maturation of sensorimotor behaviour in mice, and suggest that this conclusion may possibly be explained by the relatively recent appearance of mice in the mammalian radiation.

Agenesis of Corpus Callosum↗
PubMed1991

Antigen-specific tolerance induced by autoimmunization with photoinactivated syngeneic effector cells.

Development of a protocol that could invoke specific suppression of an undesired immune response, while sparing normal immune competence, would be of great clinical value. This report demonstrates that multiple infusions of splenocytes sensitized in vivo to sheep red blood cells (SRBC) and photoinactivated in vitro with 8-methoxypsoralen and ultraviolet A light can render a syngeneic recipient selectively unresponsive to subsequent challenge with this antigen. Mice treated in this fashion did not develop a T cell-mediated delayed type hypersensitivity (DTH) reaction to SRBC. In contrast, control mice exposed to nonimmune splenocytes pretreated in an identical manner developed a normal DTH response to SRBC, thereby demonstrating that drug and light in the absence of effector T cells were not suppressive. Inhibition of the DTH response was antigen specific, since animals rendered unresponsive to SRBC developed a normal DTH response to chicken red blood cells. Cell transfer experiments demonstrated that unprimed recipients of splenocytes from mice rendered unresponsive to SRBC could not mount a DTH reaction when challenged. Moreover, this procedure can also suppress established immunity to that antigen. The use of photoinactivated syngeneic antigen-reactive effector cells as immunosuppression agents suggests that this method may be clinically useful in inhibiting pathogenic antigen-specific immunologic reactions.

Animals↗
PubMed1991

Inhibition of anti-skin allograft immunity induced by infusions with photoinactivated effector T lymphocytes--the congenic model.

We have previously reported the capacity to produce donor-specific tolerance to alloantigens by intravenous exposure to pretreated antidonor T cells. The current study has refined this system by using congenic mice differing only at the H-2 major histocompatibility complex genetic loci. Twelve days after B10 mice received MHC-incompatible B10.D2 skin grafts, their splenocytes that included an expanded population of cells mediating rejection were treated with 100 ng/ml 8-methoxypsoralen (8-MOP) photoactivated by 1 J/cm2 of ultraviolet A prior to infusion into naive B10 recipients. Whereas 8-MOP itself is biologically inert, photoactivated 8-MOP crosslinks DNA by covalently binding to pyrimidine bases. Recipient B10 mice were tested for tolerance to B10.D2 alloantigens in mixed leukocyte culture (MLC), cytotoxicity (CTL), and to in vivo delayed type hypersensitivity assays and challenged with a fresh B10.D2 graft. In vivo, the DTH response of the pretreated B10 mice was specifically suppressed to the relevant alloantigen, correlating with retention of B10.D2 skin grafts for up to 22 days postengraftment without visual evidence of rejection, in comparison to control complete rejection of the skin graft in less than 12 days. In vitro, splenocytes from B10 recipients of pretreated syngeneic splenocytes containing large numbers of B10 anti-B10.D2 T cells proliferated less in MLC and generated lower cytotoxic T cell responses to B10.D2 alloantigens than did controls and suppressed the B10 MLC and CTL responses to B10.D2 alloantigen. These results reveal that, in a highly defined congenic transplantation system, infusions of photoinactivated effector cells resulted in selective inhibition of the in vivo responses that correlated with allograft rejection and permitted prolonged retention of histoincompatible skin grafts. This approach may have significant practical applicability for treatment of human disorders caused by aberrant T cells.

Animals↗
PubMed1991

Localization and characterization of substance P binding sites in rat and rabbit eyes.

Specific and high-affinity binding sites for Substance P (SP) were found in eyes from albino rabbits and rats using an in vitro autoradiographic method with 125I-Bolton Hunter SP (BHSP). autoradiograms were generated by apposing 10-20 microns-thick cryostat eye sections to 3H-Hyperfilm or liquid emulsion and quantified by means of image-analysis procedures. Kinetic studies showed that equilibrium was reached after a 75-min incubation at room temperature. In rat retina, specific binding corresponding to approximately 90% of total binding, was reversible, of high affinity (dissociation constant [Kd], 0.13 +/- 0.02 nM). Half-time for dissociation of 125I-BHSP was about 15 min. Unlabeled SP and the two neurokinins (NK) A and B competed in a concentration-dependent manner for retinal sites labeled by 125I-BHSP with the following order of potencies: SP greater than NKA greater than NKB, in agreement with a pharmacologic profile of a SP receptor site. In both species, specific binding was found in the iris sphincter muscle, choroid, and retina. In rats, detectable amounts of SP-binding sites were also expressed in the corneal epithelium and iridial stroma. Quantitative analysis of the autoradiograms revealed that the highest densities of 125I-BHSP binding sites were localized in the iris sphincter muscle in rabbits and the inner retina in rats.

Animals↗
PubMed1991

[Treatment of dry eye syndrome with lacrimal gel: a randomized multicenter study].

The appearance on the French market of a carbomer tear substitute, Gel-Larmes, an original galenic form, constitutes a real therapeutic progress in the treatment of dry eye syndrome. An open randomized multicentric trial was conducted comparing the tolerance and efficacy of Gel-Larmes with those of eye drops containing chondroitin sulphate. The statistical analysis evidences an inferior average number of daily instillations for Gel-Larmes, its better efficacy on the symptoms as well as on the objective criteria: biomicroscopic examination, break-up time, rose Bengal test. The tolerance of the product is excellent and 81% of the patients express their wish to pursue Gel-Larmes versus 54% for the reference product.

Acrylic Resins↗
PubMed1991

No evidence for HTLV-I infection in 24 cases of French and Portuguese mycosis fungoïdes and Sezary syndrome (as seen in France).

A survey in search of evidence for HTLV-I infection was conducted on French and Portuguese patients residing in France with a diagnosis of mycosis fungoïdes or Sezary syndrome. Methods used in this investigation included serological assays (ELISA, Western blot, particle agglutination, indirect immunofluorescence) and DNA molecular studies (Southern blot and polymerase chain reaction). Cultures of peripheral blood mononuclear cells were performed and checked by electron microscopy and reverse transcriptase assay. The results indicate that neither HTLV-I nor a closely related retrovirus are associated with mycosis fungoïde or Sezary syndrome in the cases studied.

Adult↗
PubMed1990

[Systemic mastocytosis and malignant mastocytosis].

Systemic mastocytosis is a rare, often undiagnosed disease characterized by the proliferation of mast cells in several tissues. The clinical symptoms are related to the mast cell infiltrates, but also to the release of numerous mediators. Malignant mastocytosis is a term that refers to two different entities: aggressive mastocytosis, where the outcome with a myeloproliferative disease, where the latter governs the prognosis. The potential severity of these diseases justifies the development of more intensive therapeutic measures.

Humans↗
PubMed1990

Inhibition of autoimmune disease in a murine model of systemic lupus erythematosus induced by exposure to syngeneic photoinactivated lymphocytes.

MRL/l mice develop progressive, virulent autoimmune disease that has many of the features of systemic lupus erythematosus. Prophylactic treatment of MRL/l mice with syngeneic photoinactivated autoimmune splenocytes improves survival and inhibits the fulminant hyperproliferation of abnormal T cells and the production of high titer anti-DNA antibody invariably found in untreated mice. The proliferation of Thy 1+ splenic T cells was significantly decreased, and prolonged retention of the response to T-cell mitogen was found in treated mice. Treatment with unmodified cells induced a partial inhibition of disease features which did not prolong survival rates. These results suggest that phototherapy potentiates a normal immunoregulatory process which enables suppression of the development of abnormal cell populations in young MRL/l mice with relatively intact immune systems.

Animals↗
PubMed1990

[Contrast sensitivity and diabetes].

Contrast sensitivity has been assessed in 24 diabetic patients in order to test the hypothesis that contrast sensitivity is impaired in the early stages of diabetes mellitus. All patients had 20/20 vision. Some evidence of visual dysfunction was observed in 33% of the diabetics with no retinopathy and 83% of the 6 patients with retinopathy when compared to 48 age-matched controls. Contrast sensitivity was mainly reduced in the mid-range spatial frequencies and correlated with the degree of retinopathy. The accurate assessment of visual dysfunction in diabetes is very important, as new drugs (i.e. aldose reductase inhibitors) are currently under evaluation.

Contrast Sensitivity↗
PubMed1989

Inhibition of antiskin allograft immunity by infusions with syngeneic photoinactivated effector lymphocytes.

Induction of tolerance for skin allotransplantation requires selective suppression of the host response to foreign histocompatibility antigens. This report describes a new approach that employs pretreatment of effector cells with 8-methoxy-psoralen (8-MOP) and ultraviolet A light (UVA) to render the effector cells of graft rejection immunogenic for the syngeneic recipient. Reinfusion of photodamaged cells resulted in an immunosuppressive host response that permitted prolonged retention of histoincompatible skin grafts and specifically inhibited in vitro and in vivo responses that correlate with allograft rejection. Eight days after BALB/c mice received CBA/j skin grafts, their splenocytes served as a source of alloreactive effector cells. The splenocytes were treated with 100 ng/ml 8-MOP and 1 J/cm2 UVA before reinfusion into naive BALB/c recipients. Recipient mice were tested for tolerance to alloantigens in mixed leukocyte culture (MLC), cytotoxicity (CTL), delayed type hypersensitivity assays (DTH), and challenge with a fresh CBA/j graft. Splenocytes from BALB/c recipients of photoinactivated splenocytes containing the effector cells of CBA/j alloantigen rejection proliferated poorly in MLC and generated lower cytotoxic T cell responses to CBA/j alloantigens in comparison with sensitized and naive controls. Splenocytes from these hyporesponsive mice suppressed the MLC and CTL response to alloantigen from sensitized and naive BALB/c mice. In vivo the DTH response was specifically suppressed to the relevant alloantigen in comparison with controls. Moreover, BALB/c mice treated in this fashion retained a CBA/j skin graft for up to 42 d posttransplantation without visual evidence of rejection. These results indicate that the in vivo and in vitro response to alloantigen can be attenuated by pretreating the host with photoinactivated splenocytes containing the effector cells of alloantigen rejection.

Animals↗
PubMed1989

[Vitreous hemorrhage and neovascular proliferation in multiple sclerosis].

We report the case of a 40 year-old man with multiple sclerosis, who presented a bilateral proliferative retinopathy responsible for a vitreous hemorrhage. Examination of the periphery of the retina showed diffuse retinal periphlebitis; fluorescein angiograms showed a peripheral retinal ischemic syndrome with secondary neovascularization. Several recent studies have show that retinal periphlebitis is a frequent finding in multiple sclerosis; but to our knowledge a retinal ischemic syndrome with neovascularization has seldom been reported.

Adult↗